The group A streptococci are responsible for a number of human diseases including scarlet fever, erysipelas, acute glomerulonephritis, and rheumatic fever. These organisms possess a number of different antigens and extracellular products which contribute to virulence, but no single factor is solely responsible for the virulence of the organism. It is the objective of this investigation to isolate and study the determinants for type A streptococcal exotoxin (erythrogenic toxin), streptolysin O, streptolysin S, and M protein. The type A exotoxin is responsible for the rash of scarlet fever and is known to be produced only by certain lysogenic strains of streptococci. One hypothesis to be tested in this investigation is whether non-lysogenic strains possess the ability to synthesize, perhaps in an intracellular form only the type A exotoxin. Experiments are described to elucidate the mechanism of toxigenic conversion by which lysogenic strains of Streptococcus pyogenes produce the type A exotoxin. Additional experiments will be directed to obtaining the following hemolysin determinants; plasmid-mediated hemolysin/bacteriocin, streptolysin O, and streptolysin S. These determinants will be studied to ascertain the extent of homology with one another and to estimate the epidemiological and evolutionary associations of hemolysins among various streptococci. Specific experiments are described to obtain the M protein determinant. Once obtained, this determinant should provide a source of unaltered M protein, potentially free of toxic or immunologically cross reactive components, and useful for a vaccine to prevent rheumatic fever and rheumatic heart disease. The availability of these determinants of virulence in group A streptococci will facilitate new biochemical and regulatory studies, heretofore not possible, and should aid in the clarification of their possible roles in non-suppurative sequelae of streptococcal infections such as rheumatic fever and acute glomerulonephritis.